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Qi Wu,1,* Xingxing Wu,1,* Mao Wang,2,* Kexin Liu,1 Yuge Li,1 Xiaoyu Ruan,1 Lin Qian,1 Lingchang Meng,3 Zhiting Sun,3 Lei Zhu,1 Jing Wu,3 Genglin Mu3 1Gastroenterology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Institute of Chinese Medicine, Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wu; Genglin Mu, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of the Nanjing University of Chinese Medicine, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cn; glyydwsj@163.comBackground: Baicalin is an important active flavonoid isolated from the roots of Scutellaria baicalensis (S. baicalensis), a well-known traditional Chinese herb used in treating inflammatory bowel disease (IBD). The objectives of this study were to assess the potential benefit of baicalin in experimental colitis, as well as to investigate metabolic biomarkers of experimental colitis in conjunction with network pharmacology.Methods: Using a widely utilized network pharmacology technique, baicalin’s targets and pathways were predicted. Simultaneously, experimental colitis was induced by intrarectal administration of TNBS. Histopathology examinations were performed to confirm pathological changes. Plasma samples were examined by using an untargeted metabolomics technique based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen differential metabolites and associated metabolic pathways. Additionally, network pharmacology and integrated analysis of metabolomics were used to identify the primary targets.Results: Through network pharmacology research, tumor necrosis factor (TNF), interleukin 6 (IL6), serine/threonine-protein kinase (AKT1), and other 7 proteins were found to be the main targets of baicalin against IBD. The untargeted metabolomics results showed that 47 metabolites in glycerophospholipids and sphingolipid metabolism were involved as key pathways in the experimental colitis model group. 19 metabolites, including Sphingomyelin (SM d42:2, SM d42:1, SM d34:1), Lysophosphatidic acids (LPA 18:4), 1-Palmitoylglycerophosphocholine, and 17(18)-EpETE were demonstrated as key metabolites for baicalin to exert effects. Moreover, udp-glucose ceramide glucosyltransferase (UGCG), sphingomyelin synthase 1 (SGMS1), and sphingosine kinase (SPHK1) were predicted as sphingolipids-linked targets of baicalin against experimental colitis by integrative analysis.Conclusion: Based on these results, it implies that sphingolipid metabolism and sphingolipid signaling pathway might be acted as therapeutic mechanism for baicalin against experimental colitis.Keywords: baicalin, inflammatory bowel disease, sphingolipid metabolism, metabolomics, network pharmacology, inflammation

Background: Cytochrome P450 (CYP) 46A1 enzyme is a neuro-specific metabolic enzyme that converts cholesterol to 24-hydroxycholesterol. Inhibition of CYP46A1 activity is of great significance to improve neurodegenerative disorder. Objective: The present study aimed to investigate the inhibitory effect of wolfberry dicaffeoylspermidine derivatives on CYP46A1. Methods: The inhibitory effect of six wolfberry dicaffeoylspermidine derivatives on CYP46A1 activity was investigated using cholesterol as a substrate in vitro. Molecular docking was used to simulate the interactions between wolfberry dicaffeoylspermidine derivatives and CYP46A1. Results: Of these spermidines, lycibarbarspermidines D (1) and A (2) showed highly-selective and strong inhibitory effects on CYP46A1 but not on other human CYP isoforms. Both 1 and 2 exhibit mixed partial competitive inhibition of CYP46A1, with Ki values of 106 nM and 258 nM, respectively. Notably, 1 and 2 had excellent orientations within the active cavity of CYP46A1, and both formed three water-hydrogen bonds with W732 and W765, located near the heme of CYP46A1. Conclusion: Compounds 1 and 2 showed a highly-selective and nanomolar affinity for CYP46A1 in vitro. These findings suggested that compounds 1 and 2 could be used as potent inhibitors of CYP46A1 in vitro.

Rain-like layer removal from hot-rolled steel strip surface has been proven to be a workable measure for suppressing the false alarms frequently triggered in automated visual inspection (AVI) instruments. This article extends the scope of the “rain-like layer” from dispersed waterdrops to splashing water streaks and tiny white droplets. And a targeted method with both channel-wise and spatial-wise attention, namely attentive dual residual generative adversarial network (ADRGAN), is proposed. Meanwhile, a newly updated steel surface image dataset with typical natures of a “rain-like layer” gathered from an actual hot-rolling line, Steel_Rain, is opened for the first time. The comparison of experimental results between our proposed network and 11 prestigious networks shows that our ADRGAN-restored images are the closest to the ground-truth images on six public datasets, especially on the newly opened industrial dataset Steel_Rain; it yields the best scores of 56.8627 peak signal to noise ratio (PSNR), 0.9980 structural similarity index (SSIM), 0.134 mean-square error (MSE) and 0.006 learned perceptual image patch similarity (LPIPS). In the final verification test, the concept of rain-like layer removal has been proved to perform best in defect inspection, where four traditional defect detection algorithms are involved. And as expected, defect detection methods assisted by ADRGAN yield the minimum false alarms.

Bridged carborane–anthracene dyads 1 and 2 exhibit emissions both in solution and in solid state, and blue-shifted mechanochromic luminescence.

This paper proposes a three degrees of freedom parallel anti-swing method by the main and auxiliary cables to address the problems related to underactuated double-pendulum anti-swing for a ship-mounted jib crane. By analysing the dynamic coupling relationship between the swing of the hook and the payload, it seeks to establish an accurate dynamic model of the anti-swing device under the ship’s rolling and pitching conditions, and discusses the influence of ship excitation, the crane state, load posture and anti-swing parameters on the in-plane and out-of-plane swing angles. The analysis shows that the primary pendulum reduces the in-plane angle by 90% and the out-of-plane angle by 80%, the in-plane angle of the secondary pendulum is reduced by 90%, and the out-of-plane angle is reduced by 80%. The reliability of the simulation data is verified through experiments.

Intervertebral disc (IVD) degeneration (IVDD) is a characteristic of the dominating pathological processes of nucleus pulposus (NP) cell senescence, abnormal synthesis and irregular distribution of extracellular matrix (ECM), and tumor necrosis factor-α (TNF-α) induced inflammation. Nowadays, IVD acid environment variation which accelerates the pathological processes mentioned above arouses researchers’ attention. KAN0438757 (KAN) is an effective inhibitor of selective metabolic kinase phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) that has both energy metabolism reprogramming and anti-inflammatory effects. Therefore, a potential therapeutic benefit of KAN lies in its ability to inhibit the development of IVDD. This study examined in vitro KAN toxicity in NP primary cells (NPPs). Moreover, KAN influenced tumor necrosis factor-α (TNF-α) induced ECM anabolism and catabolism; the inflammatory signaling pathway activation and the energy metabolism phenotype were also examined in NPPs. Furthermore, KAN’s therapeutic effect was investigated in vivo using the rat tail disc puncture model. Phenotypically speaking, the KAN treatment partially rescued the ECM degradation and glycolysis energy metabolism phenotypes of NPPs induced by TNF-α. In terms of mechanism, KAN inhibited the activation of MAPK and NF-κB inflammatory signaling pathways induced by TNF-α and reprogramed the energy metabolism. For the therapeutic aspect, the rat tail disc puncture model demonstrated that KAN has a significant ameliorated effect on the progression of IVDD. To sum up, our research successfully authenticated the potential therapeutic effect of KAN on IVDD and declaimed its mechanisms of both novel energy metabolism reprogramming and conventional anti-inflammation effect.

Unlike other death forms, such as autophagy, necrosis, and apoptosis, ferroptosis is a novel type of programmed cell death with iron-dependent properties. Esteroxygenase affects the content of unsaturated fatty acids and promotes lipid peroxidation. In addition, GSH can cause the reduction of GPX4, which can cause ferroptosis. P53 and its signaling pathways also regulate ferroptosis. Recent studies have confirmed that ferroptosis also promotes the death of RGC. The progressive loss of RGC is one of the pathological features of glaucoma, indicating that ferroptosis may be related to the onset of glaucoma. Down-regulation of GPX4 leads to the loss of nerve cells, which suggests that ferroptosis may also be related to diseases related to optic nerve damage. At present, ferroptosis has been extensively researched and advanced in systemic diseases, such as cardiovascular diseases, gastrointestinal tumors such as stomach, liver, and pancreas, and brain diseases. This review focuses on the research progress of ferroptosis in ophthalmic diseases, especially glaucoma and optic nerve damage.

Bacteriocins are bacterial-derived peptides that exhibit antimicrobial activity and can be used as food preservatives. Here, using the indicator strain

Background: In recent years, many naphthoquinone compounds with anticancer activity have been identified in Arnebiae Radix, and some of them have the potential to be developed into anticancer drugs. Objective: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application. Methods: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches “naphthoquinone compounds” and “anticancer”. The keywords of “shikonin” and “shikonin derivatives” were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database. Results: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity. Conclusion: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

The missile-target assignment (MTA) is a typical weapon-target assignment problem in Command and Control of modern warfare. Despite the significance of the problem, traditional algorithms still lack efficiency, solution quality, and practicability in the adversarial environment. In this article, we propose a data-driven policy optimization with deep reinforcement learning (PODRL) for the adversarial MTA. We design a comprehensive reward function to motivate the optimization of assignment policy. As such, the learned policy can implicitly model the penetration of missiles under an adversarial environment in a data-driven way. We also present a fair sample strategy to improve the sample efficiency and accelerate the policy optimization. Experimental results show that PODRL can adaptively generate satisfactory solutions in both small-scale and large-scale instances. Furthermore, we evaluate the effectiveness of PODRL in a multiobjective scenario. The result demonstrates that a well-optimized policy can achieve high-quality allocation and demand forecast of the missile resources simultaneously.

Aims. This study aims to investigate the potential biomarkers of inflammatory bowel disease (IBD) and IBD with damp-heat syndrome (IBD-DH) by metabolomics. Methods. Plasma and urine samples were collected from 15 healthy controls and 30 IBD patients, including 15 IBD-DH and 15 IBD with spleen deficiency syndrome (IBD-SD), which was coded as SF8G and SF70 according to the International Classification of Diseases Eleventh Revision (ICD-11) issued by World Health Organization. Pseudotargeted metabolomics method was used based on ultra-high-performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry. Results. Under the condition of false discovery rate (FDR) 1.0, and fold change (FC) > 1.5 or 1.0, and FC > 1.5 or

Ground-penetrating radar (GPR) is an important tool for measuring soil water content (SWC) at the field scale. The amplitude analysis of the early time signal (ETS) of GPR may provide a rapid way to estimate SWC. By assuming a homogeneous medium, various studies have been conducted on the relationship between the amplitude of ETS and the topsoil layer’s electromagnetic parameters (dielectric permittivity and conductivity) through numerical simulations, laboratory experiments, and field experiments. Soil is a typical inhomogeneous medium, and soil cultivation is a factor affecting its heterogeneity. In this context, we discuss the ability of the amplitude of ETS to estimate the water content of heterogeneous soil. First, we establish a multi-scale stochastic medium model with the inhomogeneous distribution of dielectric permittivity and conductivity and simulate the GPR response by the finite-difference time-domain (FDTD) method to observe the influence of medium heterogeneity on the GPR response. The heterogeneity of the soil models is evaluated by a geostatistical analysis described by two parameters, correlation length and variability. Then, we analyze the relationship between variability and the average envelope amplitude (AEA) of ETS. A strong soil heterogeneity increases the error of the AEA method in estimating SWC. Finally, the AEA method is used to estimate the SWC of two adjacent fields with different heterogeneities, which were caused by different cultivation methods. The results of the numerical simulation and field experiment indicate that the soil heterogeneity can have an impact on the estimation of SWC using EST, with an error lower than 3% within a depth range of 1/2 λ to λ (wavelength). This suggests that the EST of GPR can be applied to soil layers with relatively large lateral changes in water content.

AimsImmune stress in broiler chickens is characterized by the development of persistent pro-inflammatory responses that contribute to degradation of production performance. However, the underlying mechanisms that cause growth inhibition of broilers with immune stress are not well defined.MethodsA total of 252 1-day-old Arbor Acres(AA) broilers were randomly allocated to three groups with six replicates per group and 14 broilers per replicate. The three groups comprised a saline control group, an Lipopolysaccharide (LPS) (immune stress) group, and an LPS and celecoxib group corresponding to an immune stress group treated with a selective COX-2 inhibitor. Birds in LPS group and saline group were intraperitoneally injected with the same amount of LPS or saline from 14d of age for 3 consecutive days. And birds in the LPS and celecoxib group were given a single intraperitoneal injection of celecoxib 15 min prior to LPS injection at 14 d of age.ResultsThe feed intake and body weight gain of broilers were suppressed in response to immune stress induced by LPS which is an intrinsic component of the outer membrane of Gram-negative bacteria. Cyclooxygenase-2 (COX-2), a key enzyme that mediates prostaglandin synthesis, was up-regulated through MAPK-NF-κB pathways in activated microglia cells in broilers exposed to LPS. Subsequently, the binding of prostaglandin E2 (PGE2) to the EP4 receptor maintained the activation of microglia and promoted the secretion of cytokines interleukin-1β and interleukin-8, and chemokines CX3CL1 and CCL4. In addition, the expression of appetite suppressor proopiomelanocortin protein was increased and the levels of growth hormone-releasing hormone were reduced in the hypothalamus. These effects resulted in decreased expression of insulin-like growth factor in the serum of stressed broilers. In contrast, inhibition of COX-2 normalized pro-inflammatory cytokine levels and promoted the expression of Neuropeptide Y and growth hormone-releasing hormone in the hypothalamus which improved the growth performance of stressed broilers. Transcriptomic analysis of the hypothalamus of stressed broilers showed that inhibition of COX-2 activity significantly down-regulated the expression of the TLR1B, IRF7, LY96, MAP3K8, CX3CL1, and CCL4 genes in the MAPK-NF-κB signaling pathway.ConclusionThis study provides new evidence that immune stress mediates growth suppression in broilers by activating the COX-2-PGE2-EP4 signaling axis. Moreover, growth inhibition is reversed by inhibiting the activity of COX-2 under stressed conditions. These observations suggest new approaches for promoting the health of broiler chickens reared in intensive conditions.

Salmonella Typhimurium is an important zoonotic pathogen, widely distributed in nature. S . Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from Salmonella infection each year, which poses a substantial risk to public health and causes a considerable economic loss.

China's plug-in electric vehicle (PEV) market with stocks at 7.8 million is the world's largest in 2021, and it accounts for half of the global PEV growth in 2021. The PEV market in China has dramatically evolved since the pandemic in 2020: over 20% of all new PEV sales are from China by mid-2022. Recent features of PEV market dynamics, consumer acceptance, policies, and infrastructure have important implications for both the global energy market and manufacturing stakeholders. From the perspective of demand pull-supply push, this study analyzes China's PEV industry with a market dynamics framework by reviewing sales, product and brand, infrastructure, and government policies from the last few years and outlooking the development of the new government’s 14th Five-Year Plan (2021-2025). From the demand side, small-sized sedans and compact sport utility vehicles with increased electric ranges are both popular for PEVs, and the electric range of over 60% of new battery electric vehicles in 2021 has been longer than 400 km. From the supply side, although foreign brands like Tesla are still competitive, the products by Chinese domestic automakers like BYD are becoming more attractive and cannibalizing the high-end market. However, the production capacity and cost of PEVs may be limited by the upstream of the supply chain – the battery manufacturing and supply chain inflation. In addition, it is also uncertain how much sales demand impacts will be caused by the potential global economic recession. The government firmly supports electrification and decarbonization of the vehicle industry by emphasizing the importance of the vehicle industry for promoting the greenhouse gas net zero by 2060. The dual-credit policy is regarded as the most critical regulation in a bid to restrain fuel consumption and promote PEV share. Still, the market is facing some technological obstacles, such as battery safety and driving range anxiety, before real prosperity. In addition, the Chinese electric vehicle market is seeing a trend toward the development of new technologies such as vehicle-to-X, autonomous driving, and connected vehicles.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

The cultivation of rice varieties with high seed vigour is vital for the direct seeding of rice, and the molecular basis of regulation of seed vigour remains elusive. Here, we cloned a new gene OsHIPL1, which encodes hedgehog-interacting protein-like 1 protein as a causal gene of the major QTL qSV3 for rice seed vigour. OsHIPL1 was mainly localized in the plasma membrane and nucleus. RNA sequencing (RNA-seq) revealed that the ABA-related genes were involved in the OsHIPL1 regulation of seed vigour in rice. The higher levels of endogenous ABA were measured in germinating seeds of OsHIPL1 mutants and NIL-qsv3 line compared to IR26 plants, with two up-regulated ABA biosynthesis genes (OsZEP and OsNCED4) and one down-regulated ABA catabolism gene OsABA8ox3. The expression of abscisic acid-insensitive 3 (OsABI3), OsABI4 and OsABI5 was significantly up-regulated in germinating seeds of OsHIPL1 mutants and NIL-qsv3 line compared to IR26 plants. These results indicate that the regulation of seed vigour of OsHIPL1 may be through modulating endogenous ABA levels and altering OsABIs expression during seed germination in rice. Meanwhile, we found that OsHIPL1 interacted with the aquaporin OsPIP1;1, then affected water uptake to promote rice seed germination. Based on analysis of single-nucleotide polymorphism data of rice accessions, we identified a Hap1 haplotype of OsHIPL1 that was positively correlated with seed germination. Our findings showed novel insights into the molecular mechanism of OsHIPL1 on seed vigour.

In this paper, the assembly problem of circular-rectangular compound peg and hole parts in automatic assembly is proposed for the first time, and an automatic assembly method based on six-dimensional force sensor is summarized. Firstly, according to the quasi-static equilibrium condition, the contact states are summarized. It is concluded that there are 7 categories of 44 contact states in insertion stage and the forces conditions to maintain each contact state; Secondly, according to the analysis of the force/moment relationship, the jamming diagram is drawn, and the conditions of jamming are analyzed. Thirdly, the assembly strategy is discussed, including contact state recognition strategy, hole searching strategy, and pose adjustment strategy. Finally, combined with impedance control, the assembly theory is verified in ADAMS, and the assembly with minimum clearance of 0.1 mm is achieved.

MOV is often used to limit the overvoltage generated by the current breaking of DC breaker to protect power electronic device from breakdown. However, while suppressing overvoltage, the MOV also causes the degradation of continuous operating voltage capability. This paper proposes a novel solid-state switch scheme with high voltage utilization efficiency by using modular gapped-MOV (MG-MOV) for DC breakers. The breakable gap is first applied to the protection of power electronic devices. By using the gap to share the voltage in the static state and be broken down in the dynamic state, the overvoltage and continuous operating voltage of the solid-state switch can be decoupled. Moreover, based on the modular scheme, the instability of the gap breakdown and the voltage imbalance of the series devices can be solved well. The working mechanism, voltage-balance and stability issue of the MG-MOV are discussed in detail in this paper, and a 15kA prototype is developed to verify the feasibility of the novel solid-state switch scheme. The experiment results show that voltage utilization efficiency can be increased from 44.4% to 72.0% by using MG-MOV.